Ilya Bezprozvanny on Presenilin Loss of Function—Plan B for AD?

COMMENT γ-secretase and therefore not qualified to comment on the specific points raised by these authors. I would,

Grace Stutzmann on Improved calcium imaging in transgenic mice expressing a troponin C-based biosensor.

COMMENT This study introduces a transgenic mouse expressing a novel, genetically encoded calcium indicator named CerTN-L15. At first pass, the utility of the mouse met with skepticism as past attempts to endogenously express fluorescent indicators have not been p

Boris Schmidt on Intra- or intercomplex binding to the gamma-secretase enzyme. A model to differentiate inhibitor classes.

COMMENT Finally, a very sound analysis provides a model to explain the strange pharmacology of gamma-secretase modulators and inhibitors. It can even incorporate the previous report on partial active site knock-outs. 0 Schmidt_Boris

Christian Czech on Presenilin Loss of Function—Plan B for AD?

COMMENT Shen and Kelleher raise some interesting points and provide a new view to the potential pathology of AD. Is AD caused by a loss of function of presenilin? Some presenilin mutations reduce NICD levels and thus could be pathogenic by reducing Notch function

Bruce Miller on Alternative cleavage of Alzheimer-associated presenilins during apoptosis by a caspase-3 family protease.

COMMENT Interesting paper. 0 brumiller

Gregory J. Brewer on Presenilin Loss of Function—Plan B for AD?

COMMENT Shen and Kelleher present a compelling hypothesis that presenilin function is critical to the pathogenesis of AD. Alternatively, a loss of presenilin function may contribute more to the damage of calcium dynamics according to the calcium hypothesis of AD

E T on Interferon-gamma and tumor necrosis factor-alpha regulate amyloid-beta plaque deposition and beta-secretase expression in Swedish mutant APP transgenic mice.

COMMENT These new findings support the idea that glial interferon-γ and TNFα enhance Aβ deposition through BACE1 expression and suppression of Aβ clearance. They provide another piece of experimental evidence linking TNFα to AD pathogenesis. The authors conclude,

Gabrielle Strobel on gamma-cleavage-independent functions of presenilin, nicastrin, and Aph-1 regulate cell-junction organization and prevent tau toxicity in vivo.

COMMENT Note by Alzforum Editor: This paper has been retracted. According to the authors, several of the figures were found to contain serious inaccuracies and no longer support the major conclusions of the paper. Click on retraction page links for complete autho

Michael G. Agadjanyan on Immunotherapy Update: Toward Patches and Creams

COMMENT In this interesting paper, Nikolic and colleagues examined the efficacy of transcutaneous immunization (TCI) with fAβ42 and cholera toxin (CT) in induction of immune responses to Aβ and reducing cerebral amyloidosis in PSAPP mice without development of si

Erik Jansson on Aβ40—The Anti-Amyloid?

COMMENT This paper seems to skirt many years of autopsy studies finding that the senile plaques have marginal statistical capacity to distinguish normal from AD patients, such as Davis et al., 1999. Also in 1999, Lue et al. concluded that soluble Aβ posed the gre

John Trojanowski on Chronic traumatic encephalopathy in a national football league player: part II.

COMMENT Repeated traumatic brain injury (TBI) in tau transgenic mice variably induces accelerated tangle formation. Moreover, the evidence that TBI is a robust risk factor for AD is very strong; see Yoshiyama et al., 2005. 0 trojanow Enhanced neurofibrillary tang

Terrence Town on In Twist on Immunotherapy, Antibodies Stimulate Neurogenesis

COMMENT comment above that a case for functionality would be much stronger in the presence of positive

Carmela Abraham on Presenilin Loss of Function—Plan B for AD?

COMMENT Undoubtedly, the PNAS paper by Shen and Kelleher provides alternative lines of thought for the primary cause of neurodegeneration in FAD cases with presenilin mutations due to a presenilin loss of function. My question to the authors is, what is their thi

Terrence Town on Immunotherapy Update: Toward Patches and Creams

COMMENT We appreciate the comments of Drs. Lemere and Solomon. I'd like to comment on a few of the

Nikolaos K. Robakis on Presenilin Loss of Function—Plan B for AD?

COMMENT In the last years, several laboratories have shown experimentally that presenilin FAD mutations cause a loss of function in both γ-secretase-dependent (Chen et al., 2002; Marambaud et al., 2003; Georgakopoulos et al., 2006) and γ-secretase-independent (Ka